Cancer as a Metabolic Disease- Part 2

Let me introduce you to the concept of “cancer as a metabolic disease”- a term coined by Dr Thomas Seyfried! In my previous post, I highlighted the issue of obsessing with a “100% evidence base”. You might have realised that research into nutrition- at least in the past, but hopefully this will change- has to be taken with a pinch of salt and that you’ll find a study contradicting the exact same thing another study reaffirms for almost anything you investigate. It’s hair-pullingly frustrating sometimes!

You might also have read my approach that doesn’t only require taking the latest evidence on board but also- at the risk of sounding very unscientific- to combine it with our own inner wisdom or “common sense”, if that sounds more reassuring to you 🙂

And, as I already discussed on numerous occasions, in the case of a low carb or ketogenic diet for cancer, we’re exactly at that turning point (hopefully!) of science (or… eeehhmm… politics?) where current guidelines issued by governments and their organisations (like many cancer societies, for instance) are still very much pointing towards the “evidence of the food pyramid” but people- and some very smart scientists and medics- are asking for change. The tide is turning- slowly but surely. Let me tell you why!

What does “cancer as a metabolic disease” even mean?

There is also a convincing- and growing- body of research that questions the origins of cancer and whether cancer is really a genetic disease. What most of us have learned in college or elsewhere on cancer is that it originates in the DNA of a cell when a series of mutations in a single cell happen. Mutations that affect cell division (particularly those that allow cells to divide uncontrollably) can be the start of many forms of cancer. That’s why some people call cancer “a genetic disease”

For the past 50 years, this so-called “somatic mutation theory” (ie mutations that take place in non-reproductive cells) has been the prevailing paradigm in cancer research- with very limited outcomes, as we all know. An increasing number of scientists have been looking for other approaches to cancer management. What if cancer has little to do with genes but metabolism is much more important? By the way, when I talk about metabolism, I mean all chemical reactions that happen in a living organism to sustain life. In other words, it’s the way we use food, water, oxygen to heal, grow or generate energy.

One of the scientists at the forefront of the notion of “cancer as a metabolic disease” is Professor Thomas Seyfried from Boston College, who has been carrying out extensive research for many years now. He took a particular interest in so-called nuclear transfer experiments, as you can see in the graphic below (Source: Seyfried T (2015), “Cancer as a mitochondrial metabolic disease”, Front. Cell Dev. Biol. 3:43):

Normal cells are shown in green with normal nuclear and mitochondrial functions. Tumour cells are in red with abnormal nuclear and mitochondrial morphology, indicating genomic instability and damaged respiration. On the very left, we see that if a healthy cell replicates, it begets two healthy daughter cells. When a cancer cell- with cancerous nucleus and cytoplasm- divides, the result are two cancer cells. No big surprises there. But then it gets interesting: when a tumour cell nucleus is transferred into a healthy cytoplasm with well functioning mitochondria, cell replication begets two normal cells although there is genomic abnormality in the nucleus- which usually leads to cancer. Wow! On the other hand, it was observed that the transfer of a healthy nucleus into a tumour cell cytoplasm (including abnormal mitochondrial function) resulted in tumour cells (or dead cells).

For me, this is just mind blowing. It essentially means that DNA mutations alone cannot explain the origin of tumours and that healthy mitochondrial function has the potential to suppress the formation of cancer cells. I know it takes a while to let this sink in and get your head around, but consider it a very likely possibility in the origin of cancer.

The concept of the ketogenic diet

You might ask yourself now how on earth you can affect your metabolism in such a powerful way with food alone and, most importantly, ensure your mitochondria remain healthy and potentially protect your cells from turning cancerous. And this brings us to the concept of the ketogenic diet.

The structure of a biological animal or human cell. The mitochondria are the small organelles filled with orange creases (called “cristae”).

We’ve known for quite some time that cancer cells make energy in a different way than healthy cells. As I’ve shown in the graph above, there’s something going on with the powerhouses of a cell, the mitochondria, where 80-90% of our total energy is produced. Many cancer cells have damaged, ineffective (and sometimes inexistent) mitochondria, which is one of the reasons why tumour cells rely on a very archaic, inefficient and also “dirty” way of generating energy: glycolysis, the splitting of glucose. This process happens in the cytoplasm outside the mitochondria and generates a lot less energy. To compensate- as you can imagine, the energy requirements of a cancer cell are pretty high-, a cancer cell splits glucose at a very high rate.

This mechanism is probably best demonstrated in PET scans: It shows glucose consumption in tissue when a patient is injected with radioactive glucose (e.g. FDG). This is a glucose analog that is taken up very avidly by cancer cells that are aggressive. This is due to a phenomenon called the Warburg effect. Otto Warburg, a famous biochemist, demonstrated 100 years ago that aggressive cancers may be hypoxic (not using oxygen) but that even if you expose them to normal oxygen conditions, they still retain this glucose and glycolytic dependence.

In short, areas that light up in a PET scan usually show cancer cells that are outcompeting healthy tissue for glucose availability. PET scans are the gold standard for the diagnosis of many cancer types (except for prostate cancer, for instance), to determine the location and also the aggressiveness of cancer cells. The more aggressive and potentially life threatening a cancer is, the more it’s going to light up on a PET scan.

What is the rationale behind a ketogenic diet for cancer?

Because we know that many cancer cells are reliant on glucose, a ketogenic diet aims to keep blood sugar and insulin low by drastically reducing carbohydrates to about 3-10% of total calorie intake a day. The other important thing is to keep protein intake at a moderate or in some cases even low level. The first reason why this is important is glutamine. It has been shown that the amino acid glutamine can be used by certain cancer cells in an almost as efficient way as glucose- for growth and metastasis. For obvious reasons- glutamine is a non-essential amino acid and can therefore be produced by the body- we haven’t found any way of cutting out glutamine completely and I doubt there will ever be a way or drug to do this.

Also, protein can have an insulinogenic effect, which means it can induce an insulin response just like carbohydrate-rich foods. Insulin is a classic example of an anabolic hormone and many cancer cells overexpress insulin and also IGF-1 receptors. In simple words, the presence of insulin signals the cancer cells that the environment is optimal for growth and division. Insulin can also be protective of tumour cells during cancer treatments: we know that if insulin levels are low, cancer cells are more likely to be killed by radio or chemotherapy.

The many pathways targeted by the ketogenic diet

But insulin isn’t the only pathway that is targeted by the ketogenic diet, which basically mimicks a fasting state. Other important pathways in the cell like PI3 kinase, AKT, mTor and AMP kinase are also affected in a positive way for cancer patients, including those undergoing treatment. Dominic D’Agostino stated in a recent podcast that about 20 known pathways are affected by keto but that we’re only at the start of understanding the complexity of this dietary approach.

What we also know is that ketone bodies have a positive influence on the epigenome, which means the way we express our genes. Also, the growth of tumour cells can be inhibited by ketone bodies whereas healthy cells are protected from a stressful environment like for instance cancer treatment. That’s why there are numerous companies now focusing on the production of ketone salts and esters, which can help an individual go into ketosis quicker and with less side effects.

Rainer Klement, a radiation oncologist from Germany, explained in a recent interview that there are studies underway that explore the possibility of cancer patients (or any other keto candidate) having a ketogenic shake in the morning, which will then allow patients to be more relaxed with their diet for the remainder of the day. Based on his experience, radiotherapy treatment has been shown to be more effective when ketone bodies are high. Of course, taking these so-called “exogenous ketones” doesn’t have the exact same effects as being in ketosis via diet, i.e. encouraging the liver to produce (endogenous) ketone. But it’s definitely a development that I keep a very close eye on because it could make the implementation of a ketogenic diet- and indeed treatment outcomes- more successful.

How quality of life can be affected

Many cancer patients don’t only experience benefits in terms of tumour management or slowed disease progression but other improvements in general wellbeing. This is what I’ve observed on my keto journey so far:

Improved weight management– whether this is losing, maintaining or gaining weight.
In my case, I’ve put on a bit of weight (after losing some in the initial months) but I always tended to be underweight, however much I ate. My conclusion is that I probably didn’t absorb nutrients properly. I had iron and other nutrient deficiencies ever since I was first tested.

Better mood, focus and concentration; general improvement of neurological functions.
Because I don’t need to eat every 2 hours any more and my body isn’t busy digesting food on an almost non-stop basis, I find I can focus better, I have a clearer mind and get more done in less time. I’d say many keto dieters would agree on this! My mood is also more stable and it takes a lot to get me down.

Digestive health
This is a controversial one! Some doctors and nutrition experts doubt that a high fat diet can be good for our gut health. Many of them argue that a lack of beneficial fibre (from not eating enough vegetables or whole grains) can be one of the major tripping stones on a low carb or ketogenic diet. There is lots of evidence that the gut microbiome (the mini eco-system in our digestive tract) plays an absolutely crucial role in our immune system, in mental health and pretty much every system in our body.My view is the following (until I’m proven wrong, that is): I don’t think it’s necessary for anyone to stay ultra low carb (i.e. 12g net carbs) for a long time. There are lots of other strategies that can help enhance ketosis without compromising on nutrients and fibre. In my experience, most people can slowly start increasing their non-starchy veg intake once they’re fully keto adapted and therefore incorporate a larger amount of gut-friendly foods. BUT I think it’s not only a question of amount… variety is equally if not more important. By this, I mean eating lots of different colours on a regular basis, eating the greens of leeks/spring onions, broccoli stalks, “chewy” leaves of cauliflower, sprouted seeds and beans, to name just a few. If implemented in this way, I doubt there will be any problem with a lack of diversity in the gut flora. This depends on other factors, of course, but I observe that the more the body is used to burning fat, the more it takes to be moved out of ketosis. Keto-adaptation (ie teaching the body to burn fat efficiently) is a very dynamic process that needs to be monitored and adapted on a regular basis.

Hormone balance
Contrary to what you may read on thyroid and other hormone balance, I found that if somebody implements the ketogenic diet properly, monitors it regularly and investigates any side effects that last longer than a few days (e.g. sleep problems, feeling lethargic, digestive issues, menstrual irregularity), keto can be great for a “hormone reset”. In my case, this is certainly true. I also know certain practitioners that use the ketogenic diet in the very short term (6-8 weeks) to get somebody’s hormone balance back on track.

Recovery time after exercise
I only recently started to train more intensely again because I was always a bit concerned about pushing my blood glucose levels up too much when training hard. But because I’ve been in remission for over 5 years now, I’ve started to become a bit more adventurous again. For some reason, my body doesn’t respond to cardio in the same positive way it used to, and that’s why I’ve switched to weights and more resistance training. Although I push myself hard, I bounce back incredibly well and hardly ever have sore muscles the following day. I remember doing the same hard workouts and feeling sore for days afterwards when I was much younger.

Not being a slave to food
This is a biggie for me and definitely has a bit impact on my quality of life. I used to be dependent on snacks and couldn’t leave the house without food. Now I know that if needs be, I can fast for a prolonged period of time without becoming a “hangry witch”… I think my husband appreciates this even more than me 😉

Feeling somewhat in control
Last but not least, this factor simply can’t be underestimated. Call it placebo or whatever you like- it is SO important for any chronically ill patient to feel that they have a say in their future. Personally, I found treatment hard to undergo because I had absolutely no say in the regime. I was told what to do or not to do, and for anybody who is used to questioning things and wanting to be in the driver seat of their lives, this can be challenging. Following the ketogenic diet gave me something tangible to do, I was able to measure the effects and monitor progress. And I knew that there was some responsibility I could take in this tricky situation!

Why is this approach not more mainstream?

You might wonder, after reading all this and exploring the science behind a ketogenic diet, why this information is not more mainstream and why not every cancer patient is being given the option of trying a ketogenic diet. I think the main reason is that there are still many myths and misconceptions around the ketogenic diet. It is still a largely misunderstood subject and many medical professionals, for instance, still haven’t fully understood the difference between nutritional ketosis and ketoacidosis. This is starting to change, though, and I’ve recently observed that some website like for instance Diabetes UK don’t state that ketosis is a “dangerous state” any more and that they’ve corrected this section of the website.

It is undebatable that diabetic ketoacidosis is a very serious metabolic condition that can result in death. But it is also a fact that if a patient is able to produce insulin- even if it’s very small amounts- it is near impossible to end up in ketoacidosis, except if we’re in very prolonged periods of starvation, engage in prolonged severe exercise or go on alcohol binges. Insulin regulates the utilization of glucose for fuel in the cells, the flow of fatty acids and the creation of ketone bodies, as we’ve seen earlier. And that’s why it’s also so important to do certain blood tests with your doctor before embarking on a ketogenic diet!

In ketoacidosis, both glucose and ketone bodies rise to very high levels– in other words, it is unrestrained, excessive ketosis in the presence of excess glucose. Because a very high amount of the slightly acidic ketone bodies is released, they can build up in the bloodstream and overwhelm the delicate acid-base buffering system of the blood. Blood pH drops fast and if no insulin is administered to slow the ketosis and fluids are replaced, this condition can be fatal.

Nutritional ketosis, however, is very different: It is a state of low blood glucose levels and- generally- slowly rising ketone bodies because the body takes a while to adapt. The only time acidosis can be a problem is if somebody goes into ketosis very quickly, but I’ve only ever observed this phenomenon in a child. The mother was instructed beforehand on possible complications, recognized the symptoms and immediately took steps to remedy this problem.

When people sometimes ask me what I consider the most important factor when implementing the ketogenic diet, it’s this quote by Dr Westman.

Keto as the first port of call for cancer patients

We will probably never be 100% sure whether it’s true that we can consider cancer as a metabolic disease or whether it’s of genetic origin. Honestly, I truly believe that for metabolic conditions, a ketogenic diet should be the first port of call alongside conventional treatments, but that there are lots of factors influencing the rate and pace at which we go into ketosis. Behaviours, goals, discipline, social circle, the environment and others play a crucial role. Food is such a personal and emotional subject that can make the implementation of a ketogenic diet challenging or sometimes impossible. And, don’t forget that there are many variations of a low carb and ketogenic diet and if you’re determined to go this path, there are many options waiting for you.

Ready to learn more about the ketogenic diet for cancer? Hop over here!

About Patricia Daly

Patricia Daly is a fully qualified Nutritional Therapist (BA Hons, dipNT, mBANT, mNTOI) based in Dublin, Ireland. Following her cancer diagnosis, she left her corporate career and started studying nutrition, specialising in the area of Integrative Cancer Care. As a Swiss native, she regularly attends training courses in Switzerland/ Germany, including at the renowned Tumor Biology Center in Freiburg, Germany. Read More…